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Purity: ≥98%
Fuzuopali (SHR3162; Fluzoparib; Fuzuloparib) is a potent PARP [poly (ADP-ribose) polymerase] inhibitor with the potential for the treatment of solid tumours. It has been approved in China for recurrent ovarian cancer.
| ln Vitro |
BRCA2-deficient V-C8 cells and BRCA1-deficient MDA-MB-436 cells showed concentration-dependent increases in γH2AX levels in response to fluzoparib (30 μM; 24 h); however, BRCA-proficient V cells did not exhibit this effect. ‐C8#13‑5 cells [1]. In MDA-MB-436 cells, fluzoparib (10μM) activates the G2/M checkpoint by raising pCDK1 and cyclin B levels over the course of 24 hours [1]. HR-deficient MDA-MB-436 cells undergo G2/M arrest and apoptosis when exposed to fluzoparib (10 μM; 72 h), which concentration-dependently enhances caspase-3, -8, and -9 processing [1]. When it comes to HR-deficient cells, such as BRCA1-deficient cells (UWB1.289), MDA-MB-436, BRCA2-deficient cells (V-C8), BRCA1-deficient cells, BRCA2 mutant cells (MX-1), and BRCA1 hypermethylated cells, pazoparib is preferentially effective against them. The IC50 values of (OVCAR-8) cells are 0.51μM, 1.57μM, 0.053μM, 1.57μM, and 1.43μM, appropriately. Both V-C8#13-5 and UWB1.289 BRCA1 have IC50 values of greater than 10μM[1]. These cells are HR competent.
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| ln Vivo |
The pharmacokinetic characteristics of fluzoparib (oral gavage; 0.3, 1, or 3 mg/kg; single dose) in female Balb/cA nude (5–6 week old) mice harboring MDA-MB-436 are good. Fluzoparib is quickly absorbed and eliminated from the blood after a single oral dosage; within two hours, plasma concentrations of the medication quickly reach their maximal levels. On the other hand, fluzopanib concentrations in tumors (57.9 μg/g, 39.3 μg/g, and 85.6 μg/g at dosages of 0.3, 1, and 3 mg/kg) persisted even 24 hours after delivery. g), correspondingly] [1]. In nude mice, fluzoparib (oral gavage; 30 mg/kg; 21 days) does not significantly cause weight loss, but it does significantly suppress tumor growth, with an inhibition rate of 59% (day 21) at 30 mg/kg. MDA-MB-436? (deficiency in BRCA1)? model [1]. When apatinib, paclitaxel, or cisplatin were administered orally by gavage (BID; 21 days) along with fluzoparib (3 mg/kg), the corresponding growth inhibition rates were 61.4%, 55.3%, and 72.8%. On day 21, the combinations of apatinib, cisplatin, and fluzoparib or apatinib, paclitaxel, and apatinib resulted in growth suppression in vivo by 84.9% and 75.6%, respectively. Weight loss was seen with the 2-drug combination of fluzoparib and cisplatin as well as the 3-drug combination of apatinib, cisplatin, and fluzoparib; no appreciable toxicity was seen with the other combinations [1].
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| References |
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| Additional Infomation |
Fluzoparib is under investigation in clinical trial NCT03863860 (A Trial of Maintenance Treatment With Fluzoparib Versus Placebo in Relapsed Ovarian Cancer Patients).
Fuzuloparib is an orally available inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2, with potential antineoplastic activity. Upon oral administration, fuzuloparib inhibits PARP 1 and 2 activity, which inhibits PARP-mediated repair of damaged DNA via the base excision repair (BER) pathway, enhances the accumulation of DNA strand breaks, promotes genomic instability, and leads to an induction of apoptosis. The PARP family of proteins catalyze post-translational ADP-ribosylation of nuclear proteins, which then transduce signals to recruit other proteins to repair damaged DNA. PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance. |
| Molecular Formula |
C22H16F4N6O2
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| Molecular Weight |
472.395057678223
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| Exact Mass |
472.127
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| Elemental Analysis |
C, 55.94; H, 3.41; F, 16.09; N, 17.79; O, 6.77
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| CAS # |
1358715-18-0
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| PubChem CID |
56649297
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| Appearance |
White to off-white solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
748.5±70.0 °C at 760 mmHg
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| Flash Point |
406.5±35.7 °C
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| Vapour Pressure |
0.0±2.6 mmHg at 25°C
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| Index of Refraction |
1.690
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| LogP |
0.52
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
34
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| Complexity |
839
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CC=C(CC2C3C=CC=CC=3C(NN=2)=O)C=C1C(N1CC2=NC(C(F)(F)F)=NN2CC1)=O
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| InChi Key |
XJGXCBHXFWBOTN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16F4N6O2/c23-16-6-5-12(10-17-13-3-1-2-4-14(13)19(33)29-28-17)9-15(16)20(34)31-7-8-32-18(11-31)27-21(30-32)22(24,25)26/h1-6,9H,7-8,10-11H2,(H,29,33)
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| Chemical Name |
4-[[4-fluoro-3-[2-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[1,5-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one
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| Synonyms |
Fuzuloparib; SHR3162; SHR-3162; SHR 3162; Fluzoparib;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~70.55 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1169 mL | 10.5843 mL | 21.1685 mL | |
| 5 mM | 0.4234 mL | 2.1169 mL | 4.2337 mL | |
| 10 mM | 0.2117 mL | 1.0584 mL | 2.1169 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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